Celiac disease (gluten-sensitive enteropathy) is a malabsorption disorder characterized by atrophy of the small intestine and caused by intolerance to gluten (present in cereal grains such as wheat and rye). The prevalence is 1/2000 to 1/8000 in most western countries, but is about 1/350 in the West of Ireland. Fifteen affected sibships from the West of Ireland were sampled and typed for 200 highly polymorphic markers. Non-parametric affected sib-pair analysis using SIBPAL pointed to 12 genomic regions of interest; multipoint analysis of these regions pointed to three regions with a maximum lod score greater than 3.9. Once of these regions was the HLA region, already known from association studies to be involved in the disease; this locus appears to have a dominant mode of inheritance. The new region with the highest lod score (4.7)is also located on chromosome 6, about 20 cm from the HLA-linked locus, and appears to have a recessive mode of inheritance. Two-locus analyses suggests that the two interact multiplicatively to produce disease. Collection of additional families is underway.